The gene expression of a cell can be regulated by epigenetic mechanisms, i.e. by altering the physical state of the chromosomes themselves. One such epigenetic mechanism is based upon the modification of histones. Depending upon the modification, an area of the genome can be made more or less accessible to transcriptional machinery, essentially up or down regulating gene expression in that area, leading to changes in cell behavior and characteristics.
Such epigenetic mechanisms, such as histone modifications, are thought to be crucial for the survival of cancer cells, particularly metastatic cells and those which are resistant to standard therapies (Baylin, 2011, Crea et al., 2011a, Min et al., 2010, Iliopoulos et al., 2010). Therefore, combining epigenetic therapies with chemotherapy and radiation treatments may allow for more complete treatment responses.
Polycomb Repressive Complexes (PRCs) are key regulators of, e.g. histone modifications in cancer cells (Simon and Lange, 2008, Lee et al., 2006, Ben-Porath et al., 2008). PRC2 often contains EZH2, a methyltransferase that tri-methylates histone H3 at lysine 27 (H3K27me3). Accordingly, EZH2 inhibition has been identified as a possible therapeutic strategy for the treatment of cancer.